ATPS-41: DENDRITIC CELL BASED IMMUNOTHERAPY OF MALIGNANT GLIOMA VIA A NOVEL CD8α+ DC TARGETED ADENOVIRAL VECTOR

The dismal clinical prognosis of glioblastoma multiforme (GBM) and severe lack of efficacious therapies demand the development of novel strategies that can directly translate to patient care. Given their role as nature's most potent antigen presenting cells, dendritic cells (DCs) have emerged as essential targets for anti-tumor vaccination over the past four decades. However, realities have thwarted the enthusiasm of DC vaccines: the lack of specific in vivo DC-targeted delivery vehicles and an inability to induce robust effector CD8 + T cell responses have led to an underwhelming anti-tumor T cell response. To surmount this major obstacle, we analyzed DC-induced T cell activation and showed that a CD8α+ DC subset is essential for priming robust CD8 + T cells responses. Based on this understanding, we engineered a CD8α + DC selective vector, Ad5scFv205FF by incorporating a single chain antibody against DEC205 which is selectively expressed in CD8α+ DC subset. After confirming the genetic engineering of the fiber modification via PCR and Western blot analysis, we analyzed the tropism of this novel DC targeted vehicle. This DC targeted Ad5scFv205FF vector lost its natural tropism (coxsackie and adenovirus receptor expressing cells) and gained a new, DC selective tropism. Furthermore, upon subcutaneous administration, Ad5scFv205FF infected an average of 90% of the CD8α+ DCs while a mere 4% of non-DCs (CD45 + /CD11c-) were infected by Ad5scFvDEC205FF-GFP. This work collectively represents a novel anti-glioma vaccination, enhanced by the in vivo selective delivery of the tumor antigen that will provide a platform for the evaluation and translation of highly promising glioma immunotherapy strategies.